NDLI: An Acetate Prodrug of a Pyridinol-Based Vitamin E Analogue

Content Provider	Springer Nature Link
Author	Khdour, Omar M. Lu, Jun Hecht, Sidney M.
Copyright Year	2011
Abstract	To investigate of an approach to stabilize a novel pyridinol based α–tocopherol analogue (1) as a prodrug by acetylation of its phenol moiety.Biochemical indicators of oxidative stress in mitochondria were utilized to gain insight into the cytoprotective mechanism(s) of compound 1 acetate. Oxygen free radical scavenging activity was measured using DCF probe in a cultured cell model system that had been placed under oxidative stress. Lipid peroxidation was examined both in a cell-free system and in oxidatively stressed cultured cells. The bioenergetic parameters of mitochondria were evaluated by measuring mitochondrial membrane potential (Δψ$_{m}$) and the MPT.The present results suggest strongly that the antioxidant efficacy of compound 1 can be improved by using it as a prodrug. The tested prodrug has shown to be activated as a function of time, presumably due to susceptibility to enzymatic hydrolysis, and exhibits an antioxidant effect in time-dependent manner, providing a compound that is more effective than α-tocopherol acetate with regard to all protective properties studied.An effective approach to stabilize compound 1 was realized by using its acetate as a prodrug.
Starting Page	2896
Ending Page	2909
Page Count	14
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	28
Issue Number	11
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2011-07-06
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biochemistry Medical Law Pharmacy Biomedical Engineering Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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